CAJ | 학술논문

目的罗哌卡因和地塞米松聚乳酸-羟基乙酸微球小鼠坐骨神经旁包埋的药效学和药动学的研究.方法 165只雌性昆明小鼠随机均分为A.B、C三组,各组分别于坐骨神经旁包埋罗哌卡因.醋酸地塞米松聚乳酸-羟基乙酸微球(ROP-DXM-PLGA-MS)、罗哌卡因聚乳酸,羟基乙酸微球(RoP-PLGA-MS)、空白乳酸一羟基乙酸微球(PLGA-MS)400mg·kg~(-1).每组植入微球后按0.5、1、2、4、8、12 .24、36.48、72、96h时间点,以小鼠热踏板法检测小鼠埋药侧小鼠舔后足的潜伏期为痛阈指标值的变化评价微球镇痛效果,每个时间点测定5只小鼠;小鼠热踏板测定结束后摘眼球取血,采用HPLC测定给药后各时间点血浆罗哌卡因浓度.结果药效学实验表明ROP-DXM-PLGA-MS组麻醉镇痛时间达72 h以上较RoP-PLGA-MS组36h明显延长(p<0.01),空白微球未显示麻醉镇痛作用;药动学实验显示A、B两组罗哌卡因药动学参数Cmax、Tmax、AUC、MRT、t_(1/2)分别为117.8和119.8 ng·ml~(-1),24和12 h.8793.2和6861.15 ng·h·ml~(-1),43.7491和38.7743 h,65.799和46.166h.A、B、C三组均未测到地塞米松血药浓度数据,C组罗哌卡因和地塞米松血药浓度均未测到.结论罗哌卡因聚乳酸-羟基乙酸微球中包入地塞米松可明显延长罗哌卡因的麻醉镇痛作用.
목적 라고잡인화지새미송취유산-간기을산미구소서좌골신경방포매적약효학화약동학적연구.방법 165지자성곤명소서수궤균분위A.B、C삼조,각조분별우좌골신경방포매라고잡인.작산지새미송취유산-간기을산미구(ROP-DXM-PLGA-MS)、라고잡인취유산,간기을산미구(RoP-PLGA-MS)、공백유산일간기을산미구(PLGA-MS)400mg·kg~(-1).매조식입미구후안0.5、1、2、4、8、12 .24、36.48、72、96h시간점,이소서열답판법검측소서매약측소서첨후족적잠복기위통역지표치적변화평개미구진통효과,매개시간점측정5지소서;소서열답판측정결속후적안구취혈,채용HPLC측정급약후각시간점혈장라고잡인농도.결과 약효학실험표명ROP-DXM-PLGA-MS조마취진통시간체72 h이상교RoP-PLGA-MS조36h명현연장(p<0.01),공백미구미현시마취진통작용;약동학실험현시A、B량조라고잡인약동학삼수Cmax、Tmax、AUC、MRT、t_(1/2)분별위117.8화119.8 ng·ml~(-1),24화12 h.8793.2화6861.15 ng·h·ml~(-1),43.7491화38.7743 h,65.799화46.166h.A、B、C삼조균미측도지새미송혈약농도수거,C조라고잡인화지새미송혈약농도균미측도.결론 라고잡인취유산-간기을산미구중포입지새미송가명현연장라고잡인적마취진통작용.
Objective To investigate the pharmacokinetics and pharmacodynamies of poly(lactide-co-glycolide) microspheres containing ropivacaine and dexamethasone for sciatic nerve block in mice. Methods A total of 165 female mice were randomly assigned into 3 groups, namely dexamethasone-loaded ropivacaine microsphere group (group A, n=55), ropivacaine microsphere group (group B, n=55) and PLGA microsphere group (group C, n=55). The mice received surgical implantation of the corresponding preparations near the sciatic nerve at the dose of 400 mg/kg. Hot plate test was used to evaluate the anesthetic effect of these rnicrospheres at different time points after the implantation, and high-performance liquid chromatography (HPLC) was employed to determine plasma ropivacaine concentration. Results Pharmacodynamic study showed that the duration of sciatic nerve sensory block was significantly longer in group A than in group B (P<0.05). The analysis of pharmacokinetics variables demonstrated that T_(1/2) in group A was prolonged as compared with that of group B. No anesthetic effect was observed in group C. Conclusion Dexamethasone-loaded ropivacaine microspheres can significantly prolong the analgesic effect of ropivacaine in mice.